Nebulizer vibrating aperture plate drive frequency control and monitoring

ABSTRACT

A nebulizer has an aperture plate, a mounting, an actuator, and an aperture plate drive circuit ( 2 - 4 ). A controller measures an electrical drive parameter at each of a plurality of measuring points, each measuring point having a drive frequency; and based on the values of the parameter at the measuring points makes a determination of optimum drive frequency and also an end-of-dose prediction. The controller performs a short scan at regular sub-second intervals at which drive current is measured at two measuring points with different drive frequencies. According to drive parameter measurements at these points the controller determines if a full scan sweeping across a larger number of measuring points should be performed. The full scan provides the optimum drive frequency for the device and also an end of dose indication.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation application under 37 CFR § 1.53(b) ofU.S. patent application Ser. No. 14/423,046, filed Feb. 20, 2015, whichis a National Stage of PCT/EP2014/060723, filed May 23, 2014, whichclaims priority to European Patent Application No. EP13177909.2, filedJul. 24, 2013. The contents of each of these are incorporated herein byreference in their entirety.

FIELD OF THE INVENTION

The invention relates to aerosol generators or nebulizers, havingvibrating aperture plates to aerosolize medicaments.

PRIOR ART DISCUSSION

Examples of nebulizers are described in U.S. Pat. No. 6,546,927(Litherland) and EP1558315 (PARI). These disclosures include techniquesto predict the end of a liquid medicament dose on the aperture plate.These techniques are based on monitoring a parameter such as drivecurrent at different drive frequencies.

The approach taught in the Litherland document involves detecting thepresent desired frequency, and the desired frequency may for example bethe resonant frequency. Frequency is the variable that is swept, and aparameter is tracked. The tracking provides an indication of the desireddrive frequency. This may change as the dose decreases in volume. Forexample, the resonant frequency may drift from 135 kHz to 140 kHz from aloaded state to an unloaded state. In Litherland the device can reducepower supplied to the aperture plate and/or provide a user indication asthe dose is ending.

The present invention is directed towards providing improved frequencycontrol. Specifically, it is desired to improve any one or all of fasterfrequency control response to changes in conditions, less impact on thenebulisation process, and improved ability to accurately predictend-of-dose when used with patients who inhale medication at differentrates.

SUMMARY OF THE INVENTION

According to the invention, there is provided a nebulizer comprising avibrating aperture plate, a mounting, an actuator, and an aperture platedrive circuit having a controller, wherein the controller is configuredto:

-   -   measure an electrical drive parameter at each of a plurality of        measuring points each measuring point having a drive frequency;        and    -   based on the values of the parameter at the measuring points        make a determination of optimum drive frequency and also an        end-of-dose prediction,

characterized in that,

-   -   the controller is configured to perform a short scan at which a        parameter is measured at each of two or more measuring points        with different drive frequencies, and according to drive        parameter measurements at these points determine if a full scan        sweeping across a larger number of measuring points should be        performed.

In one embodiment, the short scan has fewer than five, and preferablytwo measuring points (CPt #1. CPt #2).

In one embodiment, the controller is configured to compare measurementswith tolerance ranges, and if a measurement falls outside its associatedrange a full scan is initiated. In one embodiment, the tolerance rangesare pre-defined.

In one embodiment, the short scan is performed at regular intervals.Preferably, the intervals are sub-second.

In one embodiment, the full scan has in the range of 5 to 300 measuringpoints. In one embodiment, the full scan has in the range of 100 to 300measuring points.

In one embodiment, the controller is configured to dynamically determinefrom the full scan a frequency for at least one of the short scanmeasuring points.

In one embodiment, in the controller is configured to select a frequencyvalue corresponding to lowest drive current as a frequency for a shortscan measuring point. Preferably, said lowest drive current isdetermined to correspond to a resonant frequency, and a frequency valuefor the full scan measuring point with lowest drive current is storedfor use as a short scan measuring point frequency.

In one embodiment, the parameter is aperture plate drive current.

In one embodiment, the controller is configured to, during a full scan:

-   -   dynamically perform a plurality of iterations, and    -   in each iteration compare the measured parameter against a        measurement at a previous measuring point to determine end of        dose and/or optimum drive frequency.

In one embodiment, a slope in parameter measurements is analysed todetermine said indication in each iteration. In one embodiment, a slopevalue above a threshold indicates end of dose.

In another aspect, the invention provides a method of operation of anebulizer comprising a vibrating aperture plate, a mounting, anactuator, and an aperture plate drive circuit having a controller,wherein the method comprise the steps of the controller:

-   -   measuring an electrical drive parameter at each of a plurality        of measuring points each measuring point having a drive        frequency; and    -   based on the values of the parameter at the measuring points        make a determination of optimum drive frequency and also an        end-of-dose prediction,    -   wherein the controller performs a short scan at which a        parameter is measured at each of two or more measuring points        with different drive frequencies, and according to drive        parameter measurements at these points determine if a full scan        sweeping across a larger number of measuring points should be        performed.

In one embodiment, the short scan has fewer than five, and preferablytwo measuring points (CPt #1. CPt #2).

In one embodiment, the controller compares measurements with toleranceranges, and if a measurement falls outside its associated range a fullscan is initiated.

In one embodiment, the short scan is performed at regular intervals,preferably sub-second. Preferably, the full scan has in the range of 5to 300 measuring points, preferably 100 to 300 measuring points.

In one embodiment, the controller dynamically determines from the fullscan a frequency for at least one of the short scan measuring points,and selects a frequency value corresponding to lowest drive current as afrequency for a short scan measuring point.

In one embodiment, said lowest drive current is determined to correspondto a resonant frequency, and a frequency value for the full scanmeasuring point with lowest drive current is stored for use as a shortscan measuring point frequency.

In one embodiment, the parameter is aperture plate drive current.

In one embodiment, the controller during a full scan:

-   -   dynamically performs a plurality of iterations, and    -   in each iteration compares the measured parameter against a        measurement at a previous measuring point to determine end of        dose and/or optimum drive frequency.

In one embodiment, a slope in parameter measurements is analysed todetermine said indication in each iteration Preferably, a slope valueabove a threshold indicates end of dose.

DETAILED DESCRIPTION OF THE INVENTION Brief Description of the Drawings

The invention will be more clearly understood from the followingdescription of some embodiments thereof, given by way of example onlywith reference to the accompanying drawings in which:

FIG. 1 is a diagram of a nebulizer drive circuit of the invention;

FIG. 2 is a flow diagram for operation of the controller to determinewhen a full end-of-dose scan should be performed;

FIG. 3 is a flow diagram showing the full end-of-dose scan;

FIGS. 4 to 6 are plots showing aspects of change of drive current withfrequency; and

FIG. 7 is a plot showing variation of both flow rate and current withdrive frequency.

Referring to FIG. 1 a drive circuit 1 for a nebulizer comprises anoutput drive stage 2 which provides the power required for transfer tothe nebulizer load 5. A filtering stage 3 removes undesirable electricalnoise from the drive signal, ensuring compliance with EMC requirements.

A high voltage resonant circuit (stage 4) conditions the drive signal toensure efficient coupling of power to the nebulizer load 5.

The mechanical arrangement of aperture plate, actuator and mounting maybe of the type which is known for example from our prior specificationnumbers WO2010035252 and US2012111970.

The circuit of FIG. 1 dynamically monitors drive current in order todetermine in real time the resonant frequencies (where resonantfrequencies refer to points of resonance and anti-resonance) to be usedin the determination of the optimum operating frequency of thenebulizer, and to also determine end-of-dose in an integrated fashion.

Short Scan

Referring to FIG. 2 the controller performs a short scan multiple timeseach second. This involves measuring drive current at the normal drivefrequency (CheckPoint #1, “CPt #1”), and measuring value of the drivecurrent to the aperture plate. The current tolerance is predefined. Thecurrent typically only changes when a change of state of the apertureplate from wet to dry occurs Once a change is identified, it prompts afull scan.

If CPt #1 drive current is outside the current tolerance a flag is setfor a full scan. If not, the frequency is changed to a second referencefrequency. The latter is determined according to a full scan. The drivecurrent value for the CPt #2 frequency is determined. Likewise, if it isoutside the tolerance the full scan flag is set. This loop is repeatedat regular intervals, multiple times per second.

The short scan is run at intervals in the order of every second or less.It only moves away from the normal operating frequency for less than1/1000th of a second while it measures the current at this second pointof measurement (CPt #2). This ensures that there is no discernibleinterruption of the nebulization process.

In summary, the purpose of the short scan is to determine if a full scanshould be performed. If the drive current is outside of tolerance thenthe full scan is activated in order to determine the optimum operatingfrequency and also to detect end of dose. The short scan does notinterfere with operation of the nebulizer because it measures at onlytwo frequencies. One of these is the resonant frequency. CPt #2 is aresonant frequency. In this embodiment the output drive stage 2 drivesat CPt #1 with a frequency of 128 KHz, which has been found to provide agood performance across a range of liquid viscosities.

In other embodiments it is possible that once the optimum drivefrequency is determined it will be used for CPt #1.

Full Scan

Referring to FIG. 3 the flow to implement a full scan is illustrated.The frequency is incremented in steps between 140 kHz and 160 kHz. Thestep size will change depending on the resolution required. For example,in one application only one type of nebulizer may be used, therefore asimple scan using only 10 steps may be sufficient. However in anapplication using multiple types of nebulizer, a much larger number ofsteps will be required to give higher resolution, in order todistinguish between wet and dry of the different devices.

At each point in the full scan the aperture plate drive current isdetermined. This provides a plot of drive current vs. frequency as shownin FIG. 4. A section with a steep slope is shown in a box in FIG. 4 andin more detail in FIGS. 5 and 6. In each iteration the current maximumdifferential (i.e. slope) is registered. Hence, in the first phase ofFIG. 3 the maximum differential is recorded in real time during the fullscan.

The next phase of the logic of FIG. 3 is to dynamically record theminimum drive current value (point of anti-resonance). At the end ofeach loop if the drive current is lower than that recorded for the shortscan CPt #2 the value is recorded, as is the corresponding frequency.The current value is recorded as the short scan CPt #2 drive currentvalue.

As illustrated by the final steps the slope recorded in the first phaseof this scan provides an indication of end of dose.

Importantly, this scan can be used to determine the optimum drivefrequency, as described above. Importantly, real time determination ofthe resonant frequencies gives configurable options for changingoperation of the nebulizer to the optimum drive frequency. The resonantfrequency may be used for either of the short scan measuring points.

This visual interruption in the plume due to the full scan lasts foronly 0.3 of a second. This has negligible effect on operation of thedevice.

The energy requirement of the aperture plate is directly proportional tothe impedance offered by the plate during aerosolization. The impedanceof the plate is measured by monitoring one or more electricalcharacteristics such as voltage, current, or phase difference, and inthe above embodiment, drive current.

The impedance of the plate to aerosolization is monitored at the initialdrive frequency (CPt #1) and the energy requirements can be determinedto be within required limits for correct operation of the vibrating meshnebulizer, at which point the drive may continue to operate at thisfrequency.

Alternatively, the frequency of operation of the drive circuit can beadjusted to determine the optimum operating point for the piezo-element.This can be the anti-resonance point (CPt #2 frequency), where theminimum energy consumption occurs (or an offset of this).

A higher frequency, beyond the point of anti-resonance, exists where theenergy consumption maximizes and this point is termed the point ofresonance.

These points can be used in determination of the optimum operatingfrequency for the creation of desired flow of aerosolized liquid. Thereare mechanical reasons why it is preferable not to drive at the resonantpoint, for example it may not result in the desired flow rate of thenebulizer or the desired particle size or may result in excessivemechanical stress on the aperture plate

Referring to FIG. 7, the optimum drive frequency can be determinedutilizing details of the electrical parameters captured by the full scanmethod. The determination of the point of anti-resonance (where currentis minimized) and the point of resonance (where the current ismaximized) can be used in choosing the optimum drive frequency.

The point of resonance may provide the maximum flow rate, however thisfrequency may result in undesirable stresses on the mechanicalstructure. Runtime variation in the resonance point may also result inundesirable fluctuations in flow rate at this resonance point. Equally,the use of the anti-resonance point may not be desirable as the flowrate may not be sufficient at this point. The optimum frequency may bebetween these two points and the final frequency can be a fixed offsetof one or more of these two points.

In FIG. 7 is might typically be the case that the operating frequency ischosen from the linear part between about 141 kHz and 150 kHz.

It will be appreciated that the state of aerosolization (wet/dry) can bedetermined by monitoring the rate of change of plate impedance betweenthe anti-resonance and the resonance points (or an offset thereof). Thisis implemented by determining the maximum positive rate of change ofimpedance between the two resonant frequencies. A steep or abrupt rateof change indicates that no liquid is on the plate (DRY). A flat/gentlerate of change indicates the presence of liquid (WET).

Alternatively, a sudden change in the impedance of the plate at theinitial frequency and/or the resonant (CPt #2) frequency can used as aquick method to indicate a possible change in aerosolization state (inthe short scan). This is what triggers the full scan to actuallydetermine the end of dose.

It will also be appreciated that the short scan provides much usefulinformation for real time control, but does not cause a visibleinterruption in aerosolization. The short scan is run in advance of afull scan, which can cause a visible interruption in the aerosolizationof liquid.

In summary, the software procedure implemented by the controller fordetermining the status of the nebulizer is as follows:

-   -   Multiple times each second, the software will run a short scan        (FIG. 2) to determine if a change of drive current has occurred.    -   This change in drive current can indicate that the        anti-resonance frequency and/or a change of state has occurred;        therefore a full scan (FIG. 3) is requested.    -   Upon completion of the full scan the status of the nebulizer is        updated. (Wet or Dry).

In some embodiments, the controller may initiate a full scan after apredetermined time (such as a further 5 seconds). The purpose of thisadditional scan is to record the maximum slope after the device hascompleted 5 seconds in the new state. When a device changes state, thechange in the current/slope profile is almost instantaneous. However,after an additional few seconds the new profile will have changed againslightly, due to changes in the mechanical structure of the plate, to avalue that the nebulizer will maintain over a longer period of time. Itis important to determine this stable value to ensure that the shortscan has details of the correct frequency to monitor. When prompted bythe short scan (or at predefined periods e.g. 5 seconds) the purpose ofthe predefined full scan may be to update the check points for the quickscan, as these two points may drift slightly during normal run mode.

The short scan checks the current consumption at the normal operatingfrequency and at one other point every interval (every second or less).If a change is found at either of these two frequencies the controllerwill flag a possible change of state (i.e. the device may have changedfrom wet to dry or from dry to wet). This change will result in a callof the full scan.

In one embodiment, for the full scan the algorithm calculates aslope/differential of the drive current at each frequency step. As thealgorithm steps through the frequencies, it measures the current andthen subtracts the current measurement taken 16 frequency stepspreviously using a rolling shift register.

The invention is not limited to the embodiments described but may bevaried in construction and detail.

The invention claimed is:
 1. A nebulizer, comprising: a vibratingaperture plate mounted within the nebulizer and driven by an actuator;and an aperture plate drive circuit coupled to the actuator and having acontroller, wherein the controller is configured to: measure anelectrical drive parameter at each of a plurality of measuring points,each measuring point of the plurality of measuring points beingassociated with a drive frequency output by the drive circuit; perform ashort scan at which the electrical drive parameter is measured at eachof two or more measuring points associated with different drivefrequencies; and according to drive parameter measurements at these twoor more measuring points, determine if a full scan sweeping across alarger number of measuring points should be performed after completionof a predetermined time delay.
 2. A nebulizer as claimed in claim 1,wherein the short scan has fewer than five measuring points.
 3. Anebulizer as claimed in claim 1, wherein the controller is configured tocompare measurements with tolerance ranges, and if a measurement fallsoutside its associated tolerance range, the full scan is initiated.
 4. Anebulizer as claimed in claim 3, wherein the tolerance ranges arepre-defined.
 5. A nebulizer as claimed in claim 1, wherein the shortscan is performed at regular intervals.
 6. A nebulizer as claimed inclaim 5, wherein the intervals are sub-second.
 7. A nebulizer as claimedin claim 1, wherein the full scan has five to three-hundred measuringpoints.
 8. A nebulizer as claimed in claim 7, wherein the full scan hasone-hundred to three-hundred measuring points.
 9. A nebulizer as claimedin claim 1, wherein if it is determined that the full scan should beperformed, performing the full scan after the predetermined time delay,and further wherein the controller is configured to dynamicallydetermine, from the full scan, a frequency associated with at least oneof the short scan measuring points.
 10. A nebulizer as claimed in claim9, wherein the controller is configured to select a frequency valuecorresponding to lowest drive current as a frequency for a short scanmeasuring point.
 11. A nebulizer as claimed in claim 10, wherein saidlowest drive current is determined to correspond to a resonantfrequency, and a frequency value for the full scan measuring point withlowest drive current is stored for use as a short scan measuring pointfrequency.
 12. A nebulizer as claimed in claim 1, wherein the electricaldrive parameter is aperture plate drive current.
 13. A nebulizer asclaimed in claim 1, wherein the controller is configured to, during thefull scan: dynamically perform a plurality of iterations, and in eachiteration, compare the measured electrical drive parameter against ameasurement at a previous measuring point to determine an end-of-doseindication and/or a selected drive frequency, wherein the end-of-doseindication is indicative of an end of an aerosolization cycle of thenebulizer, and wherein the selected drive frequency is a frequencybetween a resonant frequency and a non-resonant frequency.
 14. Anebulizer as claimed in claim 13, wherein the controller is furtherconfigured to determine a slope value from the comparison and identifythe end-of-dose when the slope value is above a threshold.
 15. Anebulizer as claimed in claim 1, wherein the predetermined time delay isfive seconds.
 16. A method of operation of a nebulizer comprising avibrating aperture plate mounted in the nebulizer and driven by anactuator, the actuator being coupled to an aperture plate drive circuithaving a controller, wherein the method comprises: measuring anelectrical drive parameter at each of a plurality of measuring points,each measuring point being associated with a drive frequency output bythe drive circuit; and performing a short scan at which a parameter ismeasured at each of two or more measuring points associated withdifferent drive frequencies, and according to drive parametermeasurements at the two or more measuring points, determining if a fullscan sweeping across a larger number of measuring points should beperformed after a predetermined time delay.
 17. A method as claimed inclaim 16, wherein the short scan has fewer than five measuring pointsand the full scan has five to three-hundred measuring points.
 18. Amethod as claimed in claim 16, wherein the controller comparesmeasurements with tolerance ranges, and if a measurement falls outsideits associated range, a full scan is initiated.
 19. A method as claimedin claim 16, wherein the short scan is performed at regular sub-secondintervals.
 20. A method as claimed in claim 16, wherein thepredetermined time delay is five seconds.